Our overall objective is to interrelate to a time course the systolic and diastolic overload to the myocardium with the compensatory hemodynamic and electrophysiological changes and the structural and ultrastructural alterations in lower animals and man. The thermodilution technique for determining ventricular volumes will be combined with the balloon technique for obstructing the pulmonary artery to study the hemodynamic changes of a pressure overload in the conscious dog. The following will be studied: 1) the role of the autonomic nervous system in the hemodynamic reflex produced by pulmonary arterial obstruction &/or distention; 2) the compliance of the acute and chronic pressure overload ventricle in relation to the influence of the pericardium, and the autonomic nervous system; 3. the role of norepinephrine in the pathogenesis of ventricular hypertrophy, particularly the model for HOCM. Similar studies will be performed with the aortic balloon obstruction technique. With a long-term infusion technique, a method is available for studying the humoral substances in the hypertrophy process & for testing chemical substances which may be efficacious in the therapy of heart failure. One of our major goals has been to discover the structural and ultrastructural basis for acute and chronic overload to the heart; emphasis will be placed on the: 1) intercalated disc - (multiple, widened & separated intercalated discs), 2) fractionation of the actin filaments, 3) ribosomes, 4) mitochondria, & 5) sarcoplasmic reticulum. Myocardial biopsies will be obtained from patients with diastolic ventricular overloads to relate structure with function. BIBLIOGRAPHIC REFERENCES: Laks, M.M., Morady: Norepinephrine -The myocardial hypertrophy hormone? Am. Heart J. 91(5):674-675, 1976. Blaufuss, A., Garner, D., Adomian, G.E., Criley, J.M., Laks, M.M.; Technique for serial right and left ventricular endocardial biopsy in dogs. J. Appl. Physiol. 40(5): 832-835, 1976.